Recruiting
Phase 1
Phase 2

ETX-636

Sponsor:

Ensem Therapeutics

Code:

NCT06993844

Conditions

Advanced Solid Tumors

Advanced Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

ETX-636 dose escalation

ETX-636 dose escalation in combination with fulvestrant

ETX-636 dose expansion in combination with fulvestrant

Study Details

Brief summary:

Phase 1/2, open-label study of ETX-636 in participants with advanced solid tumors

Conditions

Advanced Solid Tumors

Advanced Breast Cancer

Study ID

NCT06993844

Start date

Jun 10, 2025

Status verified date

Jun, 2026

Completion date

Dec 30, 2027

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key Inclusion Criteria:

  • Metastatic or locally advanced and unresectable solid tumor that has progressed on or after at least one available therapy.
  • Tumor harboring an activating PIK3CA mutation detected in either tumor tissue or ctDNA.
  • At least 1 measurable lesion or evaluable disease per RECIST v1.1.
  • An ECOG performance status score of 0 or 1.
  • Adequate organ function.

Additional key inclusion criterion for Parts B and C:

\- Confirmed metastatic or locally advanced HR+/HER2- breast cancer not amenable to surgical resection with curative intent and must have received at least 1 prior CDK4/6 inhibitor and at least 1 prior anti-estrogen therapy.

Key Exclusion Criteria:

  • Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied.
  • Has symptomatic brain or spinal metastases or a known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement.
  • Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2.
  • Has received treatment with any local or systemic anticancer therapy or investigational anticancer agent within 14 days prior to start of treatment.
  • Has toxicities from previous anticancer therapies that have not resolved to baseline levels with the exception of alopecia and peripheral neuropathy.
  • Has had radiotherapy outside the target tumor lesions within 14 days prior to start of treatment.

Study Design

Enrollment

233 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part A Dose Escalation Monotherapy (Advanced Solid Tumors with PIK3CA mutation)

Part A is a dose escalation monotherapy of ETX-636 in advanced solid tumors with PIK3CA mutation

experimental: Part B Dose Escalation Combination Therapy (HR+/HER2- locally advanced or metastatic breast cancer)

Part B is a dose escalation combination therapy in HR+/HER2- locally advanced or metastatic breast cancer. The study treatment will be ETX-636, a pan-mutant-selective PI3Kα inhibitor, in combination with fulvestrant (Faslodex) at a fixed dose of 500 mg IM.

experimental: Part C Dose Expansion Combination Therapy (HR+/HER2- locally advanced or metastatic breast cancer)

Part B is a dose expansion combination therapy in HR+/HER2- locally advanced or metastatic breast cancer. The study treatment will be ETX-636, a pan-mutant-selective PI3Kα inhibitor, in combination with fulvestrant (Faslodex) at a fixed dose of 500 mg IM.

Interventions

ETX-636 dose escalation

ETX-636 is a pan-mutant-selective PI3Kα Inhibitor and degrader in the form of an oral tablet that will be taken once per day in 28-day cycles, to evaluate escalating dose levels.

ETX-636 dose escalation in combination with fulvestrant

ETX-636 is a pan-mutant-selective PI3Kα Inhibitor and degrader in the form of an oral tablet. ETX-636 will be taken in combination with fulvestrant in 28-day cycles, to evaluate escalating dose levels. EXT-636 is an oral tablet that will be taken once per day. Fulvestrant will be administered as an injection 2 weeks apart in the first 28 days, followed by monthly injections.

ETX-636 dose expansion in combination with fulvestrant

ETX-636 is a pan-mutant-selective PI3Kα Inhibitor and degrader in the form of an oral tablet. ETX-636 will be taken in combination with fulvestrant in 28-day cycles, to expand selected dose levels. EXT-636 is an oral tablet that will be taken once per day. Fulvestrant will be administered as an injection 2 weeks apart in the first 28 days, followed by monthly injections.

Primary outcome measure

  • Evaluate Safety and Tolerability of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B [ Time Frame: First 28 days of treatment ]
  • Evaluate Safety and Tolerability of ETX-636 monotherapy in Part A and ETX-636 plus fulvestrant combination therapy in Part B [ Time Frame: Average of 6 months ]
  • Select the Recommended Phase 2 Dose(s) (RP2D) in Part B to be further explored in Part C (combination therapy expansion) [ Time Frame: Average of 6 months ]
  • Evaluate efficacy of ETX-636 plus fulvestrant combination therapy at the RP2D(s) in Part C [ Time Frame: Average of 6 months ]

Central Contacts and Locations

Central contacts

Janaki Parameswaran, MD

1-617-383-4993janaki.parameswaran@Ensemtx.com

Melinda Snyder

1-617-383-4993melinda.snyder-ext@Ensemtx.com

Locations

Hoag Memorial Hospital Presbyterian

Recruiting

Newport Beach, California, United States, 92663

Contacts

Angela J Fuller

949-764-4891aj.fuller@hoag.org

Principal Investigator:

Monica Mita, MD

UCSF Helen Diller Family Comprehensive Cancer Center

Recruiting

San Francisco, California, United States, 94158

Contacts

Phu Lam

415-818-7994Phu.Lam@ucsf.edu

Principal Investigator:

Varun Monga, MD

Yale University, Yale Cancer Center

Recruiting

New Haven, Connecticut, United States, 06520

Contacts

Carl Brown

203-785-4095carl.brown@yale.edu

Principal Investigator:

Adriana Kahn, MD

Beth Israel Deaconess Medical Center

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Susan Gotthardt

617-975-7452sgotthar@bidmc.harvard.edu

Principal Investigator:

Gerburg Wulf, MD

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

CT.GOV Contact

877-338-7425

Principal Investigator:

Sarah Simmons, MD

Carolina BioOncology Institute

Recruiting

Huntersville, North Carolina, United States, 28078

Contacts

Hannah Wall

980-441-1148hwall@carolinabiooncology.org

Principal Investigator:

Neel Gandhi, MD

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Jordi Rodon Ahnert, MD, PhD

713-792-5603

Principal Investigator:

Jordi Rodon Ahnert, MD, PhD

START

Recruiting

San Antonio, Texas, United States, 78229

Contacts

Isabel Jimenenz, RN, MSN

210-593-5265isabel.jimenez@startresearch.com

Principal Investigator:

Amita Patnaik, MD, FRPC

NEXT

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Maybelle De La Rosa

703-783-4518mdelarosa@nextoncology.com

Principal Investigator:

Alex Spira, MD, PhD, FACP

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

Contacts

Kaysey Hermens

206-667-5715khermens@fredhutch.org

Principal Investigator:

Jennifer M Specht, MD

More Information

Sponsor

Ensem Therapeutics

Last update posted

Jun 23, 2026

Last verified

Jun, 2026

Keywords

  • cancer
  • breast cancer
  • solid tumors
  • PIK3CA
  • PI3Kα inhibitor
  • Breast Neoplasms
  • Neoplasms by Site
  • Neoplasms
  • Breast Diseases
  • HER2-negative breast cancer
  • HR-positive breast cancer
  • Gynecologic cancer
  • Endometrial cancer
  • Ovarian cancer
  • Cervical cancer
  • Head and neck cancer
  • Head and neck squamous cell carcinoma
  • Fulvestrant
  • Antineoplastic Agents
  • PI3Kα
  • PI3K alpha
  • PI3Kα mutation
  • Alpelisib
  • Estrogen Receptor Antagonists
  • Estrogen Antagonists
  • Hormone Receptor Antagonists
  • Hormone Antagonists
  • Hormones, Hormone Substitutes, and Hormone Antagonists
  • Physiological Effects of Drugs
  • PIK3CA mutation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Ensem Therapeutics on 2026-06-23.